The deleterious effects of vascular-associated disorders such as stroke, heart attack, and artheroseclerosis are thought to be caused, at least in part, by the inappropriate triggering of a vascular inflammation and repair response. The vascular inflammation and repair response involves adhesive interactions between various cell types normally found freely circulating in blood. Examples of such interactions the interaction that can occur between platelets, leukocytes and the inner wall of blood vessels (i.e., the vascular endothelium). Under conditions of high fluid shear forces, platelets adhere to the endothelium via an interaction between the glycoprotein (GP) Ib-IX-V complex on their surface and von Willebrand factor (vWF) present on exposed vessel subendothelium. In contrast, leukocytes can adhere either directly to activated endothelium or indirectly by first adhering to vWF-immobilized platelets. In both instances, leukocyte cell surface molecules that bind to either the selectins or integrins classes of adhesion receptors mediate these adhesion events. Leukocyte-platelet adhesion is thought to occur, in part, via interaction of the leukocyte surface integrin molecule, MacI and the GP1b component of the platelet surface GP1b-IX-V complex.
In response to vascular disturbances such as artherosclerotic plaque rupture or mechanical injury, e.g., such as that caused by angioplasty, stent placement, ischemic damage or stenosis, leukocytes and platelets can accumulate at a vascular lesion site and provide multiple adhesive substrates for one another. This accumulation of leukocytes and platelets lead to the local production of factors including, e.g., mitogens, cytokines and chemokines, causing the further undesirable progression of a vascular disease.